Abstract
CD100 or Sema4D is a protein from the semaphorin family with important roles in the vascular, nervous and immune systems. It may be found as a membrane bound dimer or as a soluble molecule originated by proteolytic cleavage. Produced by the majority of hematopoietic cells including B and T lymphocytes, natural killer and myeloid cells, as well as endothelial cells, CD100 exerts its actions by binding to different receptors depending on the cell type and on the organism. Cell-to-cell adhesion, angiogenesis, phagocytosis, T cell priming, and antibody production are examples of the many functions of this molecule. Of note, high CD100 serum levels has been found in inflammatory as well as in infectious diseases, but the roles of the protein in the pathogenesis of these diseases has still to be clarified. Macrophages are highly heterogeneous cells present in almost all tissues, which may change their functions in response to microenvironmental conditions. They are key players in the innate and adaptive immune responses and have decisive roles in sterile conditions but also in several diseases such as atherosclerosis, autoimmunity, tumorigenesis, and antitumor responses, among others. Although it is known that macrophages express CD100 and its receptors, few studies have focused on the role of this semaphorin in this cell type or in macrophage-associated diseases. The aim of this review is to critically revise the available data about CD100 and atherosclerosis, with special emphasis on its roles in macrophages and monocytes. We will also describe the few available data on treatments with anti-CD100 antibodies in different diseases. We hope that this review stimulates future studies on the effects of such an important molecule in a cell type with decisive roles in inflammatory diseases such as atherosclerosis.
Highlights
Reviewed by: Suowen Xu, University of Rochester, United States Klaus Ley, La Jolla Institute for Allergy and Immunology (LJI), United States
It is known that macrophages express CD100 and its receptors, few studies have focused on the role of this semaphorin in this cell type or in macrophage-associated diseases
Vascular inflammation is triggered by a collection of infiltrating inflammatory cells such as monocytes, macrophages, T lymphocytes and dendritic cells, in addition to vascular smooth muscle cells (VSMCs), extracellular matrix (ECM) proteins, lipids, and calcium deposits [3]
Summary
Atherosclerosis is one of the most prevalent diseases in the world and the main cause of myocardial infarction and stroke [1]. MCD100 is involved in the interaction between different cell types It mediates platelet-platelet and platelet EC contact, favoring thrombus formation [36]; it increases monocyte-endothelial cell interaction (both of which express CD100 and its receptors). The soluble molecule shed by macrophages promotes tumor angiogenesis [44], and sCD100 released by platelets in thrombus may interact with endothelial cells, monocytes and other platelets [36]. To this date the effect of sCD100 shed by macrophages in neoangiogenesis inside atherosclerotic plaques has not been addressed, we believe this may be another important outcome of this molecule in plaque development This hypothesis is strengthened by the fact that, as already mentioned, the double KO mice for CD100 and ApoE presented less neovascularization in aortic plaques, what can be true in human disease [63].
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